Fructus mori polysaccharide alleviates diabetic symptoms by regulating intestinal microbiota and intestinal barrier against TLR4/NF-κB pathway

Fructus mori polysaccharide (FMP) has a variety of biological activities. In this study, the results showed that FMP alleviated hyperglycemia, insulin resistance, hyperlipidemia, endotoxemia, and high metabolic inflammation levels in type 2 diabetic (T2DM) mice. Next, it was found that the above beneficial effects of FMP on diabetic mice were significantly attenuated after antibiotics eliminated intestinal microbiota (IM) of mice. In addition, FMP suppressed intestinal inflammation and oxidative stress levels by inhibiting the activation of the TLR4/MyD88/NF-κB pathway, and indirectly upregulated the expression of the tight junction proteins Claudin-1, Occludin, and Zonula occlusionn-1 (ZO-1) to repair the intestinal barrier. Interestingly, the protective effect of FMP on the intestinal barrier was also attributed to its regulation of IM. The 16S rRNA and Spearman correlation analysis showed that FMP could repair the intestinal barrier to improve T2DM by remodeling specific IM, especially by significantly inhibiting 93.66 % of endotoxin-producing Shigella and promoting the proliferation of probiotic Allobaculum and Bifidobacterium by 16.31 % and 19.07 %, respectively. This study provided a theoretical support for the application of FMP as a novel probiotic in functional foods for diabetes.